Research Study on Whether a Combination of 2 Medicines (NNC0194 0499 and Semaglutide) Works in People With Non-alcoholic Steatohepatitis (NASH)

Completed · Phase 2 · Has a placebo group

Conditions studied: Non-alcoholic Steatohepatitis

In brief

This study is being done to see if a combination of 2 medicines (called NNC0194-0499 and semaglutide) can reduce liver damage in patients with non alcoholic steatohepatitis (NASH). NNC0194-0499 is a new medicine which works in the liver. Semaglutide is a well-known medicine, which is already used by doctors to treat type 2 diabetes in many countries. It also helps with weight loss and may reduce liver damage, and so prevent future liver complications. It works in a different way to NNC0194 0499. The 2 medicines may work better together than on their own. The study will also look at a combination of semaglutide and another weight-loss medicine called NNC0174-0833, which may be another treatment option for NASH. Each week, participants will get 2 injections. These could be 2 of the 3 medicines OR 1 of the medicines and a placebo OR 2 placebo injections. Which treatment participants get is decided by chance. A placebo is a dummy medicine which looks like the real medicine but doesn't contain any active medicine. The study will last for about 19 months. Participants will have 14 clinic visits and 9 phone calls with the study doctor. Participants will have 1 or 2 liver biopsies (tiny pieces of liver tissue) - one at the start (if participants have not had a biopsy recently) and one at the end of the study treatment. Women: Women cannot take part if pregnant, breast-feeding or planning to become pregnant during the study period.

Key facts

Study ID: NCT05016882
Run by: Novo Nordisk A/S
People needed: 698
Starts: 2021-08-31
Expected to finish: 2025-03-14
Last updated by the study team: 2025-11-19

Who can join

Age: any. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Aged greater than or equal to 18 years at the time of signing informed consent. In Republic of Korea, subjects must be aged greater than or equal to 19 years. In Japan, subjects must be aged greater than or equal to 20 years. In Singapore, subjects must be aged greater than or equal to 21 years.
Histological evidence of NASH based on a central pathologist evaluation of the baseline liver biopsy. The baseline liver biopsy can be a historical biopsy obtained within 180 days prior to Visit 1.
Histological evidence of fibrosis stage 2, 3 or 4 according to the NASH CRN classification based on a central pathologist evaluation of the baseline liver biopsy.
Histological non-alcoholic fatty liver disease (NAFLD) activity score (NAS) greater than or equal to 4 for subjects with F2/F3 or greater than or equal to 3 for subjects with F4 based on a central pathologist evaluation of the baseline liver biopsy. All subjects must have a score of 1 or more in steatosis, lobular inflammation and hepatocyte ballooning.

You may not qualify if…

Documented causes of chronic liver disease other than NAFLD.
Positive HBsAg, positive anti-HIV, positive HCV RNA at screening (V2A) or any known presence of HCV RNA or HBsAg within 2 years of screening (V2A).
Presence or history of ascites more than grade 1, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis or liver transplantation at V2A.
For subjects with F4, presence or history of gastro-oesophageal varices more than or equal to grade 2 at V3. An oesophagogastroduodenoscopy performed no more than 52 weeks prior to V3 must be available at V3.
Known or suspected excessive consumption of alcohol (more than 20 g/day for women or more than 30 g/day for men) or alcohol dependence (assessed by the Alcohol Use Disorders Identification Test (AUDIT questionnaire)).
Treatment with vitamin E (at doses more than or equal to 800 IU/day) or pioglitazone or medications approved for the treatment of NASH which has not been at a stable dose in the opinion of the investigator in the period from 90 days prior to V2A. In addition, for subjects with a historical liver biopsy taken more than 90 days prior to V2A, treatment should be at a stable dose in the opinion of the investigator from time of biopsy until V2A.
Treatment with GLP-1 RAs within 90 days prior to V2A. Subjects with a historical liver biopsy taken more than 90 days prior to V2A are excluded if they receive treatment with GLP-1 RAs from time of biopsy until V2A.
Treatment with glucose-lowering agent(s) (other than GLP-1 RAs), lipid-lowering medication or weight loss medication not stable in the opinion of the investigator in the period from 90 days prior to V2A. In addition, for subjects with a historical liver biopsy taken more than 90 days prior to V2A, treatment should be at a stable dose in the opinion of the investigator from time of biopsy until V2A.

Where it is running

The Institute for Liver Health — Chandler, Arizona, United States
Inst-Liver Hlth dba AZ Liver H — Peoria, Arizona, United States
Del Sol Research Management, LLC — Tucson, Arizona, United States
Hope Clinical Research — Canoga Park, California, United States
UCSD NAFLD Research Center — La Jolla, California, United States
OM Research LLC — Lancaster, California, United States
Digestive Hlth Res of SoCa — Long Beach, California, United States
Stanford Medicine — Redwood City, California, United States
UC Davis Hlth -Midtwn Ambu Cen — Sacramento, California, United States
Peak Gastro Assoc-Col Springs — Colorado Springs, Colorado, United States
Hartford Hsptl_Hartford — Hartford, Connecticut, United States
Integrity Clinical Research, LLC — Doral, Florida, United States
Miguel Rebollar PA — Hialeah, Florida, United States
Nature Coast Clinical Research_Inverness — Inverness, Florida, United States
UF Hlth Jacksonville — Jacksonville, Florida, United States
Florida Research Institute, LLC — Lakewood Rch, Florida, United States
ClinCloud,LLC — Maitland, Florida, United States
Optimus U, Corp — Miami, Florida, United States
Univ of Miami/Schiff Ctr — Miami, Florida, United States
Covenant Metabolic Specialists LLC — University Park, Florida, United States
ClinCloud, LLC — Viera E., Florida, United States
Florida Medical Clinic Orlando Health — Zephyrhills, Florida, United States
Florida Medical Clinic, LLC — Zephyrhills, Florida, United States
Piedmont Healthcare — Atlanta, Georgia, United States
North AL Health Res, LLC — Huntsville, Alabama, United States

Full record on ClinicalTrials.gov

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